Our goal is to understand how frontal cortex controls smooth pursuit eye movements. Previous work has elucidated other regions involved in reflexive pursuit. However, when cognition intervenes, frontal lobe circuitry likely participates. We have developed a pursuit go/nogo paradigm that exploits cognitive functions often deficient in patients with frontal lobe damage, such as rule encoding, set shifting and decision making, in an effort to differentiate functions of frontal structures in pursuit control. Both the supplementary eye field (SEF) and frontal eye field (FEF) are differentially active during the paradigm, and our fMRI results in humans and preliminary single-unit data in monkey suggest that ventrolateral prefrontal cortex (VLPFC) is also. We propose to determine how these regions interact in the decision to execute or withhold a pursuit movement in the context of a rule. Aims are: 1) Characterize SEF and FEF encoding of a rule-based oculomotor "if" decision 2) Investigate SEF and FEF involvement in the evolution of a rule-based "when" signal 3) Determine the role of the VLPFC in mental set-switching PUBLIC HEALTH RELEVANCE Our research will provide insight into the neuronal pathways that underlie cognitive oculomotor function in the normal oculomotor system, to allow diagnosis of frontal cortical damage in patients who have cognitive disorders. We have also done fMRI work to provide a linkage between monkey and human brain regions. This work should aid in translating our stimuli towards use in the diagnosis process.